Evaluation of Remdesivir for Preventing Severe COVID-19 in Asymptomatic or Paucisymptomatic SARS-CoV-2-Positive Kidney Transplant Recipients

The primary objective of this study is to evaluate the clinical efficacy of administering intravenous **remdesivir** for 10 days in asymptomatic or paucisymptomatic kidney transplant recipients who are SARS-CoV-2-positive by nasopharyngeal PCR or RAT within 5 days prior to the transplant. This is clinically relevant as it aims to prevent the progression to severe COVID-19 in a vulnerable population, potentially reducing morbidity and mortality associated with the infection in kidney transplant recipients.

Secondary objectives include:

• Describing the cumulative mortality at days 28 and 90 post-transplant in asymptomatic or paucisymptomatic SARS-CoV-2-positive kidney transplant recipients receiving a 10-day course of remdesivir.
• Describing the duration and severity of COVID-19 symptoms in kidney transplant recipients undergoing a peri-transplant 10-day course of remdesivir.
• Describing the clearance kinetics of SARS-CoV-2 infection in the post-transplant period and evaluating the emergence of viral resistances to remdesivir.
• Describing the incidence of graft complications, including delayed graft function, acute rejection, and graft loss at 28 and 90 days, in the specified patient population.
• Evaluating the safety profile of remdesivir in asymptomatic or paucisymptomatic SARS-CoV-2-positive kidney transplant recipients receiving the treatment.

The clinical trial involves a study population of **kidney transplant recipients** who are **SARS-CoV-2-positive** by nasopharyngeal PCR or RAT within 5 days prior to the transplant. The trial includes both male and female participants, aged 18 years and older, who are asymptomatic or have mild acute **COVID-19** symptoms, excluding fever or shortness of breath. Participants must have received at least three doses of the SARS-CoV-2 vaccine, with the last dose administered at least three months prior. The trial population was selected from patients with end-stage kidney disease on the local transplant waiting list or those scheduled to receive a non-cadaveric donor kidney transplant. Participants are required to understand the trial information and provide informed consent. Females of childbearing potential must agree to use effective contraceptive methods during the study. The sponsor has not provided the total number of participants involved in this trial.

The clinical trial is designed to evaluate the **safety** and efficacy of a 10-day course of **remdesivir** in preventing severe **COVID-19** in asymptomatic or paucisymptomatic kidney transplant recipients. This is a single-arm, proof-of-concept interventional trial, categorized as Phase 4. The trial will involve administering intravenous **remdesivir** to participants who are SARS-CoV-2-positive by nasopharyngeal PCR or RAT within five days before the transplant. The trial is expected to start recruitment on June 2, 2025, and conclude by December 1, 2027.

The trial will include an initial screening visit to confirm eligibility, which requires participants to be at least 18 years old, on a kidney transplant waiting list, and SARS-CoV-2-positive. Participants must have received at least three doses of a SARS-CoV-2 vaccine, with the last dose administered at least three months prior. The study will exclude individuals with fever or shortness of breath in the 48 hours preceding the trial. The primary endpoint is the number and proportion of participants developing severe **COVID-19** up to 28 and 90 days post-transplant. Secondary endpoints include mortality rates, symptom resolution times, and the incidence of adverse events.

Participants will be involved in the study for a maximum of 90 days post-transplant, with follow-up visits scheduled at days 0, 5, 10, 14, 21, and 28 to monitor **SARS-CoV-2** status and any emerging symptoms. The end-of-study visit will occur at day 90. Conditions that may lead to early termination from the study include severe adverse reactions to the treatment or withdrawal of consent. The trial will ensure that all female participants of childbearing potential use effective contraception and undergo pregnancy testing at enrollment. The study aims to provide valuable insights into the use of **remdesivir** in a specific patient population, contributing to the broader understanding of **COVID-19** management in immunocompromised individuals.

The clinical trial involves the administration of **remdesivir**, marketed under the name Veklury, as the experimental medication. Veklury is provided in the form of a powder for concentrate, which is then prepared as a solution for infusion. The pharmaceutical form is specifically a **solution for infusion**, and the medication is administered via **intravenous infusion**. The dosage regimen for this trial includes a maximum daily dose of 200 mg, with a total maximum dose of 1100 mg over the course of the treatment. The treatment period is set for a maximum of 10 days. Remdesivir is classified as an antiviral agent, specifically an adenosine nucleotide prodrug, and is chemically synthesized. The product is manufactured by Gilead Sciences Ireland Unlimited Company and holds the marketing authorization number EU/1/20/1459/002.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed as a single-arm proof-of-concept interventional study, focusing on the safety and efficacy of a 10-day course of remdesivir in preventing severe COVID-19 in asymptomatic or paucisymptomatic SARS-CoV-2-positive kidney transplant recipients. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial aims to evaluate the clinical efficacy of remdesivir in this specific patient population, with the primary objective of preventing the progression to severe COVID-19.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the number and proportion of participants who develop severe **COVID-19** following kidney transplantation, evaluated up to 28 days and 90 days post-transplant. Severe SARS-CoV-2 is defined by hypoxemia (O2 saturation <94%), the presence of one or more compatible respiratory symptoms (such as fever, dyspnea, increased respiratory frequency >22, cough), and new radiologic infiltrates compatible with COVID-19 as observed in chest X-ray, chest CT, or ultrasound.

Secondary endpoints include several parameters: the number of deaths at days 28 and 90 post-transplantation, both globally and attributable to COVID-19; the time to resolution and alleviation of all targeted symptoms through days 28 and 90; the duration of targeted COVID-19 symptoms; the proportion of participants requiring hospitalization extension beyond post-operative day 10; the number of days spent in hospital and intensive care unit (ICU); and the proportion of participants experiencing symptomatic rebound through day 28. Additionally, the trial will measure the number and proportion of participants with negative nasopharyngeal SARS-CoV-2 PCR results, and median CT values if positive, at various timepoints including POD 0, POD5, POD10, POD14, POD21, and POD28. Whole genome sequencing of SARS-CoV-2 will be conducted to evaluate the emergence of substitutions associated with resistance to **remdesivir** in participants with positive SARS-CoV-2 PCR and CT values below or equal to 25.

Further secondary endpoints include the number and percentage of participants with stage 2 or 3 acute kidney injury (AKI) through day 28, or renal replacement therapy (RRT) dependence at days 28 and 90; the number and proportion of patients presenting with biopsy-proven acute humoral or cellular rejection at days 28 and 90 post-transplant; and the difference in the number, proportion, and days of dialysis per patient needed at days 7, 28, and 90 compared to a local historical cohort of kidney transplants performed between 2023 and 2024. The incidence of serious adverse events (SAEs) and adverse events (AEs) leading to drug discontinuation will also be monitored, including any treatment-emergent hepatic AEs, such as elevation in ALT or AST levels, prothrombin time or INR, or blood bilirubin, as well as the number and proportion of severe liver failures. Additionally, the number of patients developing hypersensitivity or infusion-related reactions will be recorded.